TNF-alpha Gene Polymorphism and its Association with Osteoarthritis in Pakistani Patients

Abstract

Osteoarthritis (OA) is musculoskeletal degenerative synovial joint disorder, including knee, hand, spine, hip and foot, characterized by loss of joint function and synovial proliferation due to changes in the joints, which include formation of osteophytes, joint space narrowing, subchondral sclerosis, bone marrow lesions and loss of articular cartilage; consequently, causing pain in the joints. The damage in the joint is due to the contributions of certain risk factors, including female gender, increased age, obesity, any related trauma, and genetics. Many Single Nucleotide Polymorphisms (SNPs) in the TNF-α gene are reported to be involved in the onset and progression of different diseases. So, the present case-control study was designed to explore the association of -308G>A SNP in TNF- α region with the OA disease susceptibility in a Pakistani population. PCR-RFLP method was used for the genotyping of -308G>A polymorphism in 70 OA patients and 38 healthy controls. Homozygous mutant genotype AA was found more prevalent in the control group as compared to the patients, and wild type genotype GG was found more prevalent among OA patients. Statistically significant difference in the allele frequencies of patients and control individuals was observed and P value was calculated to be significant (P = 0.0001). Baseline characteristics were also studied for validating the relationship with the disease, including age, sex and BMI. In result, OA was found more prevalent in women, individuals with increased age and increased BMI values. The genotyping analysis at molecular level explains the negative association of variant allele and concludes that -308G>A polymorphism is not associated with the OA susceptibility in Pakistani population. This study was performed for the first time, so, further analysis with larger sample size is required to validate the results for this SNP in Pakistani as well as other populations.